recent Publications
Dennison, T.J. et al., 2020
Formulation and Bioequivalence Testing of Fixed-Dose Combination Orally Disintegrating Tablets for the Treatment of Tuberculosis in the Paediatric Population.
J Pharm Sci. 2020 Oct; 109(10): pp.3105-3113.
Abstract: Tuberculosis (TB) is believed to affect around 10 million people worldwide. Treatment for TB includes isoniazid and rifampicin, with fixed-dose combination (FDC) recommended for improved patient compliance. Similarly, orally disintegrating tablets (ODTs) are an increasingly popular dosage form that aid compliance since they do not require swallowing. In this study ODTs of isoniazid and rifampicin, either as discrete or FDC doses, were formulated and bioequivalence between single and combination doses compared using in vitro and in silico approaches. Dissolution profiles were compared using FDA advised difference (f1) and similarity (f2) testing in biorelevant media. Rifampicin release from FDCs decreased by approximately 15% in fed-state media (failed f1 and f2), which was attributed to enhanced rifampicin degradation in the presence of isoniazid at lower pH. Apparent permeability (Papp) values derived from Caco-2 transport studies were included alongside dissolution results into a physiologically based pharmacokinetic (PBPK) model, to simulate in vivo bioavailability in healthy subjects. Models showed no difference in bioavailability between formulations or dosing (fasted or fed) state, despite the failures in dissolution-based bioequivalence testing, highlighting shortcomings in f1 and f2 assessment and the strength of PBPK models.
Smith, J. and Marks, C., 2017
In-use microbiological assessment of caffeine citrate 10 mg/mL oral solution.
Eur J Hosp Pharm. 2018 Oct; 25(e2): e130-e133.
Abstract
Objectives: This study was conducted to investigate the microbial contamination of caffeine citrate 10 mg/mL oral solution (CCOS) during a simulated in-use test in a clinical environment.
Methods: A real-time in-use simulation study was conducted in a neonatal intensive care unit at a UK National Health Service hospital. Following the simulation, samples of the product were taken and assessed for microbiological contamination.
Results: This study shows that CCOS does not comply with the European Pharmacopoeia (Ph Eur) Specification for Preservative Efficacy. However, it shows that the in-use contamination of the product in a clinical environment remained within the Ph Eur General Text (5.1.4) Specification for the Microbiological Quality of Non-Sterile Pharmaceutical Preparations.
Discussion: There is a requirement for medicines to be developed and formulated specifically for paediatric use. This requires that excipients should be kept to a minimum. CCOS has been specifically developed to treat apnoea of prematurity in neonates. This product does not contain antimicrobial preservatives. It is produced as a terminally sterilised solution to enable an appropriate shelf-life. CCOS is currently marketed as a unit dose product, and once opened has an immediate-use, single-patient requirement. This gives CCOS an expensive unit cost. A suitable in-use shelf-life would reduce unit dose costs.
Conclusions: The evidence from this study would suggest that CCOS, a product specifically formulated for use in neonates without antimicrobial preservatives, can safely be assigned a 7-day room temperature in-use shelf-life.
In-use microbiological assessment of caffeine citrate 10 mg/mL oral solution - PubMed (nih.gov)
Martin C.J., et al., 2017
Development and Evaluation of Topical Gabapentin Formulations.
Pharmaceutics. 2017 Sep; 9(3): 31.
Abstract
Topical delivery of gabapentin is desirable to treat peripheral neuropathic pain conditions whilst avoiding systemic side effects. To date, reports of topical gabapentin delivery in vitro have been variable and dependent on the skin model employed, primarily involving rodent and porcine models. In this study a variety of topical gabapentin formulations were investigated, including Carbopol® hydrogels containing various permeation enhancers, and a range of proprietary bases including a compounded Lipoderm® formulation; furthermore microneedle facilitated delivery was used as a positive control. Critically, permeation of gabapentin across a human epidermal membrane in vitro was assessed using Franz-type diffusion cells. Subsequently this data was contextualised within the wider scope of the literature. Although reports of topical gabapentin delivery have been shown to vary, largely dependent upon the skin model used, this study demonstrated that 6% (w/w) gabapentin 0.75% (w/w) Carbopol® hydrogels containing 5% (w/w) DMSO or 70% (w/w) ethanol and a compounded 10% (w/w) gabapentin Lipoderm® formulation were able to facilitate permeation of the molecule across human skin. Further pre-clinical and clinical studies are required to investigate the topical delivery performance and pharmacodynamic actions of prospective formulations.
Development and Evaluation of Topical Gabapentin Formulations (nih.gov)